The objectives of this proposal is to develop methods for estimating the contributions of the pathways of ethanol metabolism in man. Toward this end, the approach is to be tested using a perfused rat liver system. First, whether acetaldehyde is metabolized in the liver, other than in the cytosol will be assessed. For this, the fate of the R and S hydrogens can be traced with 3H, but this necessitates two separate perfusions (or administrations to man). Therefore, it will be determined if 2H can besubstituted for 3H in the labeling of the R hydrogen. If so, (R-1-2H) ethanol and (S-1-3H)ethanol will be perfused simultaneously. The contribution of MEOS and/or catalase to ethanol's initial oxidation will be estimated from the fate of the R hydrogen of ethanol compared to the hydrogen bound to carbon 2 of sorbitol. Whether (2-2H) sorbitol can be used in place of (2-3H) sorbitol will be determined. Sorbitol is assumed to be oxidized solely via NADH for the estimation. To determine if this assumption is justified, the fate of the hydrogen of sorbitol will be compared with the fate of 3H of (2-3H) lactate.